Project Abstract The STOP and STOP II studies provided the first comprehensive stroke prevention strategy in Sickle Cell Disease supported by Class I evidence. While the strategy of TCD screening and prophylactic transfusion was very efficacious in the Stroke Prevention in Sickle Cell Anemia (STOP trial), and reversion to high risk or stroke was observed if this therapy is removed even after 30 or more months of transfusion (STOP II) it is unclear how effective this approach is in real world practice after the trials were completed. This project leverages the enormous financial and human resources expended to obtain STOP and STOP II data, and their resulting data bases (available to the investigators) with information on over 3400 children, by making an in-depth analysis of the medical records of study participants in the post trial period regarding stroke prevention behaviors (re-screening with TCD and transfusion) and stroke as well as other important outcomes. Two outcomes are of paramount interest: 1) stroke - in this respect were the strokes that took place after the trial the result of screening failures (no TCD or inadequate timing or compliance with screening programs) or treatment failures (transfusion not recommended or accepted or breakthrough stroke despite compliance with adequate transfusion) and how can this information be best used to improve stroke prevention practices; 2) conversion to high risk TCD. The data bases contain preliminary (pre abnormal) TCD data on over 3000 children, and probabilities for conversion have been published from STOP based on rescreening during the trail. Assuming varying degrees of rescreening in clinical practice post trial, and new abnormals identified post trial; does the post trial model predicting the incidence of abnormal TCD confirm STOP or vary substantially from what was observed in STOP? In either case post trial experience will be combined with STOP data to formulate stronger evidence based clinical guidelines for re screening with TCD (if the first TCD does not indicate need for treatment) to insure adequate surveillance for stroke risk. STOP and STOP II were carried out in specialized pediatric SCD centers, the impact of transition to adult provider systems on stroke prevention will be studied, attitudes assessed and these data used to inform recommendations for further research and education. Overall the project provides substantial new information that will insure the major investment made in STOP and STOP II is used to best advantage in real world applications to prevent stroke in children with SCD.